The objective of this application is to assess, in human posterior parietal cortex (PPC), the efficacy of both microwire-based array technology and decoding algorithms for neural prosthetic applications. An outcome of this work is a human-approved microwire array technology capable of reaching deep sulcal areas of the cortex. In animals, the posterior parietal cortex is an area that we have shown to encode both the reach target (goal) location and real time dynamics in point-to-point arm reaching tasks. It is our intention to show that, in the human, these features are also encoded and that goal and dynamic information can be combined for more accurate decoding of movement intentions. In addition, our research with animals has demonstrated that the PPC encodes a number of cognitive variables that could be potentially useful for neural prosthetic applications. Tasks will be designed to see if these cognitive signals can also be recorded and decoded from human PPC. These tasks will examine 1) rapid decoding of movement sequences; 2) decoding higher level aspects of goal information that are symbolic and non-spatial; 3) local field potentials to increase decode accuracy and provide a foundation for cognitive state decoding; 4) context decoding; 5) learning as a function of practice for goal and trajectory decoding and 6) learning novel effecter dynamics. We hypothesize that these cognitive aspects of animals' PPC are also available in the corresponding human PPC. Our five year goal for this grant is to complete the preclinical testing for an investigational device exemption (IDE) to the Food and Drug Administration, submit and gain approval for an IDE, obtain IRB approvals and design the behavioral tasks and data analysis that will be used in subsequent human clinical studies, and perform a clinical trial with two subjects. To this end, we have put forth five specific aims: (1) to perform a biocompatibility assessment of the technology per recommended standards, (2) to perform a histological assessment of the technology following chronic implantation, (3) to perform a safety and efficacy assessment in a non-human primate model, (4) to test the performance of decoding algorithms that will be used in humans, and (5) to assess the performance of our technology and cognitive decoding algorithms in paralyzed individuals under an FDA approved Investigational Device Exemption Clinical Trial. PUBLIC HEALTH RELEVANCE: This application has direct relevance to public health since its goal is to perform clinical trials to test a neuroprosthetic medical device for implantation in posterior parietal cortex. The clinical trials are designed to help patients with severe paralysis, which can result from spinal cord lesion and other traumatic accidents, peripheral neuropathies, amyotrophic lateral sclerosis, multiple sclerosis, and stroke.